Perspective Metz, Baker, Schymanski et al.
Figure 6. Ion mobility spectrometry separations of a mixture of sodiated pentasaccharides. The pentasacchsarides cellopentaose (blue, collision cross section [CCS] 250 Å2
), maltopentaose (red, CCS 253 Å2 mannopentaose (green, CCS 256 Å2 ) and ) were measured as their sodiated
forms using (A) an Agilent 6560 ion mobility spectrometry-quadrupole TOF and (B) a 31-m Structures for Lossless Ion Manipulations (SLIM)- TOF arrangement. The additional features (i.e., peak shoulders) can be putatively assigned to either different sodium cation binding locations or separation of α and β anomers. Estimating that roughly six peaks can fit in the SLIM-TOF separation space, the resolution of the measurement is at least less than half the difference between two of the sugars. The cellopentaose/maltopentaose and maltopentaose/mannopentaose pairs each differ by approximately 1% in CCS, and the cellopentaose/ mannopentaose pair differs by approximately 2% in CCS. The additional features resolved in the SLIM separation show a resolution of at least less than 0.5% difference in CCS.
Future perspective Unsurprisingly, some analytical and data processing challenges remain for full-scale implementation of IMS in standard exposomics workflows, including dealing with the annotation of adducts and dimers separated by DTIMS in untargeted analysis, which need to be reconciled with the principal monoisotopic ion for cor- rect annotation. Similarly, the nature of the DTIMS separation necessitates an ion gating or trap-and-release mechanism that entails a loss of duty cycle and (in the latter case) the possibility of losses of ions or interactions between different ions in the trapping environment. As such, careful analytical method development must be pursued in practice to validate the robustness and mini- mize the false annotation potential for exposome studies.
The next generation of IMS instrumentation: structures for lossless ion manipulations A current limitation of DTIMS technology is its limited resolution for a given fixed length drift tube, and since resolution is proportional to the length of the device for a given weak electric field [118], making the devices longer than several meters is not practical. Recently, ultra-high resolution IMS devices were constructed with Structures for Lossless Ion Manipulations (SLIM), utilizing travel- ing waves. In their present form, SLIM are ion conduits formed by confining electric fields using a pair of parallel printed circuit boards. Radiofrequency potentials pre-
39 Bioanalysis (2017) Bioanalysis (2017) 9(1), 81–98(1)
vent ion losses to the circuit boards and direct current potentials prevent lateral ion losses. SLIM has separated isomers from multiple molecular classes, including pep- tides, natural products, lipids and oligosaccharides that have not been fully resolved with currently available IMS systems. In initial evaluations, SLIM has separated compounds with differences in CCS < 0.5% (Figure 6). Recently, a 13-m length, serpentine path SLIM device was shown to have about fivefold higher resolution sepa- rations than present commercially available DTIMS or TWIMS platforms [119]. SLIM research at Pacific North- west National Laboratory currently focuses on multipass separations where it should be possible to obtain reso- lutions at least fivefold higher than the current SLIM, with a reasonable number of passes (<50), and a future vision includes km-long path length devices. Though the separation resolution is increased, the sensitivity of these SLIM measurements is maintained. In addition, when coupled with TOF MS, SLIM separations are still car- ried out on a rapid (∼1s) time scale, providing the oppor- tunity for ultra-high throughput studies. Traveling wave separations are the result of the abili-
ties of ions to keep up with a direct current wave push- ing them throughout the drift cell while undergoing collisions with the drift gas. Ions with larger CCS will be passed over by traveling waves more frequently than ions with smaller CCS. Due to this mechanism, the resulting separation is not linearly correlated to CCS, and the Mason Schamp equation does not hold. Thus, one caveat of TWIMS-based SLIM devices is that they do not allow for direct measurement of CCS. TWIMS does allow for calibration of CCS against standards that have been measured by DTIMS; however, calibrant ions should be from the same biomolecule class, should over- lap in m/z space and should have the same charge states as the target ions, otherwise large errors in CCS (e.g., up to >5%) can result [82,120–123]. However, since accurate CCSs are measured from the DTIMS workflow, the identified compounds can be used as internal calibrants for SLIM measurements. Importantly, SLIM should allow CCS measurements to be made for many more mixture components and with greater precision due to the far greater resolution achieved [124], and potentially allowing CCS with much greater accuracy as better stan- dards are developed. In this manner, small molecules that are not distinguishable by present DTIMS should be much better separated in SLIM-based IMS-MS and assigned with more accurate CCS values in a combined DTIMS/SLIM-MS pipeline, allowing more effective identification. Although the initial cost of devices and data management will be expensive, the time cost for measurement would be much lower than the tradi- tional targeted/suspect screening using LC-MS/MS or GC-MS/MS analysis.
future science group
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58
